Evidence map›Paper›PMID 22610140›Full record

ArticleNature immunology2012

Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization.

Haixia Xu, Jimmy Zhu, Sinead Smith, Julia Foldi, Baohong Zhao, Allen Y Chung, Hasina Outtz, Jan Kitajewski, Chao Shi, Silvio Weber and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 264 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
264citing papers in PubMed, 1 pooled it
11.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

264 citing papers in PubMed, 1 synthesis or guideline pooled it, 430 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Role of DLL4 in Neutrophil Aging and Impaired Clearance in Sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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204 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 2 countries.

Haixia XuArthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York, USA.
Jimmy Zhu
Sinead Smith
Julia Foldi
Baohong Zhao
Allen Y Chung
Hasina Outtz
Jan Kitajewski
Chao Shi
Silvio Weber
Paul Saftig
Yueming Li
Keiko Ozato
Carl P Blobel
Lionel B Ivashkiv
Xiaoyu Hu
Hospital for Special Surgery · USCornell University · USColumbia University Irving Medical Center · USKiel University · DEMemorial Sloan Kettering Cancer Center · USEunice Kennedy Shriver National Institute of Child Health and Human Development · US

Funding

Gene Regulation In The Immune SystemZIAHD001310 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI OZATO, KEIKO · 2009 to 2025
$15.0M
Inhibition of STAT3 and inflammatory cytokine productionR01AI044938 · NIAID · HOSPITAL FOR SPECIAL SURGERY · PI IVASHKIV, LIONEL B · 2000 to 2025
$9.2M
Fc Receptors &Cytokine Balance in Rheumatoid ArthritisR01AR050401 · NIAMS · HOSPITAL FOR SPECIAL SURGERY · PI Lionel B Ivashkiv · 2004 to 2026
$7.4M
Negative Regulation of OsteoclastogenesisR01DE019420 · NIDCR · HOSPITAL FOR SPECIAL SURGERY · PI IVASHKIV, LIONEL B · 2008 to 2022
$6.0M
Selective regulation of macrophage activationR01AR056729 · NIAMS · HOSPITAL FOR SPECIAL SURGERY · PI HU, XIAOYU · 2010 to 2014
$1.9M
Regulation of Osteoclastogenesis and Arthritic Bone Resorption by RBP-JK99AR062047 · NIAMS · HOSPITAL FOR SPECIAL SURGERY · PI ZHAO, BAOHONG · 2012 to 2013
$187k
NIAID NIH HHS R01 AI044938NIAMS NIH HHS K99 AR062047NIAMS NIH HHS R01 AR050401NIAMS NIH HHS R01 AR056729NIDCR NIH HHS R01 DE019420
6 · The paper itself

Abstract

Emerging concepts suggest that the functional phenotype of macrophages is regulated by transcription factors that define alternative activation states. We found that RBP-J, the main nuclear transducer of signaling via Notch receptors, augmented Toll-like receptor 4 (TLR4)-induced expression of key mediators of classically activated M1 macrophages and thus of innate immune responses to Listeria monocytogenes. Notch-RBP-J signaling controlled expression of the transcription factor IRF8 that induced downstream M1 macrophage-associated genes. RBP-J promoted the synthesis of IRF8 protein by selectively augmenting kinase IRAK2-dependent signaling via TLR4 to the kinase MNK1 and downstream translation-initiation control through eIF4E. Our results define a signaling network in which signaling via Notch-RBP-J and TLRs is integrated at the level of synthesis of IRF8 protein and identify a mechanism by which heterologous signaling pathways can regulate the TLR-induced inflammatory polarization of macrophages.

Indexed as

AnimalsCell PolarityDNA-Binding ProteinsFemaleGene Expression RegulationImmunoglobulin J Recombination Signal Sequence-Binding ProteinInflammationInterferon Regulatory Factor-8Interferon Regulatory FactorsInterleukin-1 Receptor-Associated KinasesListeriosisMacrophage ActivationMacrophagesMaleMiceMice, Inbred C57BLDNA-Binding ProteinsElf4 protein, mouseImmunoglobulin J Recombination Signal Sequence-Binding ProteinInterferon Regulatory Factor-8Interferon Regulatory FactorsInterleukin-1 Receptor-Associated KinasesMknk1 protein, mouseProtein Serine-Threonine KinasesRbpj protein, mouseReceptors, NotchTlr4 protein, mouseToll-Like Receptor 4Transcription Factors

Identifiers

PMID22610140
PMCPMC3513378
OpenAlexW2170621724

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.